Pharmacological Characterization of IW-1973, a Novel Soluble Guanylate Cyclase Stimulator with Extensive Tissue Distribution, Antihypertensive, Anti-Inflammatory, and Antifibrotic Effects in Preclinical Models of Disease.

Soluble guanylate cyclase (sGC), a key signal-transduction enzyme, increases the conversion of guanosine-5'-triphosphate to cGMP upon binding of nitric oxide (NO). Endothelial dysfunction and/or reduced NO signaling have been implicated in cardiovascular disease pathogenesis and complications of diabetes and have been associated with other disease states and aging. Soluble guanylate cyclase (sGC) stimulators are small-molecule drugs that bind sGC and enhance NO-mediated cGMP signaling. The pharmacological characterization of IW-1973 [1,1,1,3,3,3-hexafluoro-2-(((5-fluoro-2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl) pyrimidin-4-yl)amino)methyl)propan-2-ol], a novel clinical-stage sGC stimulator under clinical investigation for treatment of heart failure with preserved ejection fraction and diabetic nephropathy, is described. In the presence of NO, IW-1973 stimulated sGC in a human purified enzyme assay and a HEK-293 whole cell assay. sGC stimulation by IW-1973 in cells was associated with increased phosphorylation of vasodilator-stimulated phosphoprotein. IW-1973, at doses of 1-10 mg/kg, significantly lowered blood pressure in normotensive and spontaneously hypertensive rats. In a Dahl salt-sensitive hypertension model, IW-1973 significantly reduced blood pressure, inflammatory cytokine levels, and renal disease markers, including proteinuria and renal fibrotic gene expression. The results were affirmed in mouse lipopolysaccharide-induced inflammation and rat unilateral ureteral obstruction renal fibrosis models. A quantitative whole-body autoradiography study of IW-1973 revealed extensive tissue distribution and pharmacokinetic studies showed a large volume of distribution and a profile consistent with predicted once-a-day dosing in humans. In summary, IW-1973 is a potent, orally available sGC stimulator that exhibits renoprotective, anti-inflammatory, and antifibrotic effects in nonclinical models.

Patients’ perception about opioids and addiction in South Korea

Background@#Chronic pain affects approximately 22% of the world’s population. Opioids can be useful in chronic pain management. However, some patients have negative perception of opioids. The purpose of this research was to evaluate patients’ perception about opioids and investigate problems associated with prescribing and taking opioids in South Korea. @*Methods@#Patients who visited a pain clinic in 14 university hospitals of South Korea from September through October 2018 were asked to complete anonymous questionnaires about taking opioids. @*Results@#Of the 368 patients that were surveyed (female 53.3%, male 46.7%), 56.8% were prescribed opioids. In the opioid group, 92.8% patients had heard of opioids from their doctor and 72.6% of them had a positive perception about opioids. The side effects associated with opioid use were constipation (35.4%), dizziness (24.6%), nausea and vomiting (17.4%), dysuria (6.2%), and addiction (2.0%). In the no opioid group, the primary sources of information about opioids were doctors (49.2%), mass media (30.8%), and the internet (16.2%). The main reasons why 39.0% patients did not take opioids were fear of addiction (57.7%) and side effects (38.5%). There were 71.5% and 60.9% patients in the opioid and no opioid group, respectively, who wished to take opioids when their numeric rating scale pain score was ≥ 7. @*Conclusions@#Perception of opioids among patients who take them was either neutral or positive. However, 39.0% patients who have not been prescribed opioids did not want an opioid prescription, citing fear of addiction and side effects as the primary reasons.

Self-Forgiveness Moderates the Effects of Depression on Suicidality

OBJECTIVE@#Not all depressive individuals are suicidal. An increasing body of studies has examined forgiveness, especially self-forgiveness, as a protective factor of suicide based on that suicide is often accompanied by negative self-perceptions. However, less has been studied on how different subtypes of forgiveness (i.e., forgiveness-of-self, forgiveness-of-others and forgiveness-of-situations) could alleviate the effects of depression on suicide. Hence, this study examined forgiveness as a moderator of depression and suicidality.@*METHODS@#305 participants, consisted of 87 males and 218 females, were included in the study. The mean age was 41.05 (SD: 14.48; range: 19–80). Depression, anxiety, and forgiveness were measured through self-report questionnaires, and suicidal risk was measured through a structuralized interview. Moderations were examined through hierarchical regression analyses.@*RESULTS@#Depression positively correlated with suicidality. Results of the hierarchical regression analysis indicated forgiveness as a moderator of depression on suicidality. Further analysis indicated only forgiveness-of-self as a significant moderator; the effects of forgiveness-of-others and forgiveness-of-situation were not significant.@*CONCLUSION@#These findings suggest that forgiveness-of-self is essential in reducing of the effects of depression on suicidality. It is suggested that self-acceptance and the promotion of self-forgiveness should be considered as an important factor when developing suicide prevention strategies.

Screening Tool for Anxiety Disorders: Development and Validation of the Korean Anxiety Screening Assessment

OBJECTIVE: This study evaluated the psychometric properties of the Korean Anxiety Screening Assessment (K-ANX) developed for screening anxiety disorders. METHODS: Data from 613 participants were analyzed. The K-ANX was evaluated for reliability using Cronbach’s alpha, item-total correlation, and test information curve, and for validity using focus group interviews, factor analysis, correlational analysis, and item characteristics based on item response theory (IRT). The diagnostic sensitivity and specificity of the K-ANX were compared with those of the Beck Anxiety Inventory (BAI) and Generalized Anxiety Disorder 7-item scale (GAD-7). RESULTS: The K-ANX showed excellent internal consistency (α=0.97) and item-total coefficients (0.92–0.97), and a one-factor structure was suggested. All items were highly correlated with the total scores of the BAI, GAD-7, and Penn State Worry Questionnaire. IRT analysis indicated the K-ANX was most informative as a screening tool for anxiety disorders at the range between 0.8 and 1.6 (i.e., top 21.2 to 5.5 percentiles). Higher sensitivity (0.795) and specificity (0.937) for identifying anxiety disorders were observed in the K-ANX compared to the BAI and GAD-7. CONCLUSION: The K-ANX is a reliable and valid measure to screen anxiety disorders in a Korean sample, with greater sensitivity and specificity than current measures of anxiety symptoms.

Radiation safety: a focus on lead aprons and thyroid shields in interventional pain management

C-arm fluoroscopy is useful equipment in interventional pain management because it helps to guide correct needle targeting for the accurate injection and drug delivery. However, due to increased use of C-arm fluoroscopy in various pain procedures, the risk of radiation exposure is a significant concern for pain physicians. The harmful biological effects of ionizing radiation on the human body are well known. It is therefore necessary to strive to reduce radiation exposure. Lead aprons with thyroid shields are the most fundamental radiation protective devices for interventional procedures, and are very effective. However, the operator's radiation safety cannot be guaranteed because pain physicians seem to lack sufficient interest, knowledge, and awareness about radiation safety. Also, inappropriate care and use of radiation protective devices may result in a higher risk of radiation exposure. The purpose of this article was to review the literature on radiation safety with a focus on lead aprons and thyroid shields and present recommendations related to those devices during C-arm fluoroscopic-guided interventions by pain physicians.

Effect of Smoking Cessation Program for Workers in Large Size Company: Using Motivational Enhancement Counseling / 산업간호학회지

PURPOSE: The purpose of this study was to examine effects of smoking cessation program in large size company using motivational enhancement counseling. METHODS: A quasi-experimental design was conducted. 72 workers in intervention group and 65 workers in control group participated in 7 large size companies. Smoking cessation program consisted of a campaign, smoking cessation education, and 6 weeks motivational enhancement counseling. The motivational enhancement counseling was tailored to the individual's stage of change. Stages of smoking behavior, smoking cessation rate, nicotine dependence, and confidence of smoking cessation were assessed after intervention. RESULTS: The results showed that intervention had a significant impact on improving stages of smoking behavior and smoking cessation rate, and impact on decreasing nicotine dependence, compared to those of a control group. CONCLUSION: The effects and feasibility of smoking cessation program including motivational enhancement counseling were revealed in the large size company. These results might provide information that can be used in improving cultures of smoking cessation for workers.